Small activating RNA induces myogenic differentiation of rat adipose-derived stem cells by upregulating MyoD

ABSTRACTPurpose:RNA activation (RNAa) is a mechanism of gene activation triggered by promoter-targeted small double stranded RNAs (dsRNAs), also known as small activating RNAs (saRNAs). Myogenic regulatory factor MyoD is regarded as the master activator of myogenic differentiation cascade by binding to enhancer of muscle specific genes. Stress urinary incontinence (SUI) is a condition primarily resulted from urethral sphincter deficiency. It is thus expected that by promoting differentiation of adipose-derived stem cells (ADSCs) into myoblasts by activating MyoD gene through RNAa may offer benefits to SUI.Materials and Methods:Rats ADSCs were isolated, proliferated in vitro, and identified by flow cytometry. Purified ADSCs were then transfected with a MyoD saRNA or control transfected. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to detect MyoD mRNA and protein expression, respectively. Immunocytochemical staining was applied to determine the expression of desmin protein in transfected cells. Cell viability was measured by using CellTiter 96® AQueous One Solution Cell Proliferation Assay kit.Results:Transfection of a MyoD saRNA (dsMyoD) into ADSCs significantly induced the expression of MyoD at both the mRNA and protein levels, and inhibited cell proliferation. Desmin protein expression was detected in dsMyoD treated ADSCs 2 weeks later.Conclusion:Our findings show that RNAa mediated overexpression of MyoD can promote transdifferentiation of ADSCs into myoblasts and may help treat stress urinary incontinence (SUI)–a condition primarily resulted from urethral sphincter deficiency.

Incontinência urinária de esforço: relação familiar e predisposição genética / Stress urinary incontinence: familial relatioship and genetic predisposition

A origem multifatorial da incontinência urinária de esforço (IUE) abrange: idade, sexo, paridade, índice de massa corpórea (IMC), hipoestrogenismo e constipação intestinal, entre os mais conhecidos. Também há relatos sobre possível predisposição familiar à IUE, além de sua associação com doenças do colágeno. Baseados nesses relatos e sabendo da importância do colágeno na constituição da musculatura lisa e dos tecidos fasciais de sustentação pélvica, pode-se supor que haja predisposição genética à doença, relacionada principalmente ao metabolismo do colágeno. Alterações desse metabolismo poderiam estar envolvidas na suscetibilidade e na gênese da IUE. Os autores discutem, neste artigo, os principais trabalhos que destacam essa hipótese, o papel do colágeno e a sua relação com IUE, além das pesquisas que podem trazer aplicações práticas na prevenção e tratamento dessa doença.

The multifactorial origins of stress urinary incontinence (SUI) includes: age, sex, parity, body mass index (BMI), hipoestrogenism and intestinal constipation, among the most known factors. There are also reports about a possible familial predisposition to SUI and its association to collagen diseases. Based on these reports, and also on the collagen importance for the smooth muscles and fascial tissues constitution for pelvic organs support, it is reasonable to assume that there is a genetic predisposition to the disease, mostly related to the collagen metabolism. Changes in collagen metabolism might be involved in the susceptibility and origins of SUI. In this article, the authors discuss the main publications that may justify this hypothesis, the collagen function and its relation to SUI. The researches that may lead to practical applications for prevention and treatment of this disease are highlighted.

Mutação no exon 20 do gene da elastina em mulheres com incontinência urinária de esforço decorrente de fatores extrínsecos à uretra / Mutation in exon 20 elastin women with extra urethral stress urinary incontinence

A incontinência urinária de esforço (IUE) é uma condição de alta prevalência em mulheres, representando um problema de saúde pública. Indícios de que desordens difusas do tecido conectivo, talvez de origem genética, possam estar implicadas na gênese da IUE têm sido descritos, como maior prevalência dessa afecção em mulheres com síndromes genéticas / Stress urinary incontinence (SUI) is a high prevalent condition in women and represents a public helth problem. It has been described signs that diffuse disorders of connective tissue, perhaps by genetic causes, may be involved in SUI genesis, as increased prevalence in women with others affections, such as varicose veins and hernia...